Serious deep mycosis such as invasive candidiasis often becomes a fatal disease. Originally, it has been considered that a principal protective mechanism on the side of a host organism to Mycomycetes such as Candida would be nonspecific immunization by neutrophils. When this protective mechanism normally functions, there is a little risk of becoming infected with Mycomycetes. However, in recent years, a risk of developing deep mycosis has been increased because of increase in the number of patients with underlying diseases decreasing the immunological function of an organism, such as malignant tumors (in particular, hemopoietic malignant tumors such as acute leukemia or malignant lymphoma) or AIDS, heavy use of anticancer agents or immunosuppressive agents, heavy use of antibacterial antibiotics or steroid hormone, long-term use of central venous hyperalimentation or venous catheterization, and so on (Rinsho to Biseibutsu (Clinics and Microorganisms), vol. 17, p. 265, 1990).
The number of agents applied to a treatment for such deep mycosis is much smaller than that of antibacterial agents. There are only 6 types of agents, such as amphotericin B, flucytosine, miconazole, fluconazole, itraconazole, and micafungin.
Amphotericin B has an extremely strong fungicidal action to Mycomycetes. However, at the same time, it has a problem regarding strong side effects such as nephrotoxicity, and therefore, to use the agent in a clinical situation is limited. In addition, flucytosine has a problem that the agent causes rapid development of resistance when it is chronically used. Accordingly, at present, this agent is seldom used singly. Micafungin has a low activity to the Cryptococcus species. Other agents are generically called azole antifungal agents in terms of their structural characteristics. There is a general tendency that the fungicidal action of these agents to Mycomycetes is poorer than that of amphotericin B. However, considering both effectiveness and safety, azole antifungal agents are most frequently used at present ((Rinsho to Biseibutsu (Clinics and Microorganisms), vol. 21, p. 277, 1994).
Currently, fluconazole-resistant Candida albicans (C. albicans) has been detected with a high frequency of 30% or more in oropharyngeal candidiasis lesion of AIDS patients to whom fluconazole had been repeatedly administered. Moreover, most of the resistant strains show cross resistance to itraconazole and other azole agents. Furthermore, separation of the resistant strains has also been reported regarding non-AIDS patients who developed chronic mucocutaneous candidiasis or deep candidiasis (Rinsho to Biseibutsu (Clinics and Microorganisms), vol. 28, p. 57, 2001).
Thus, if a limited number of agents have a problem regarding resistance, it will inevitably affect the management of patients with deep mycosis, the number of which is being increased (Rinsho to Biseibutsu (Clinics and Microorganisms), vol. 28, p. 51, 2001).
Accordingly, it is strongly desired that an antifungal agent will be developed, whose action mechanism differs from those of the existing agents and which has effects on Mycomycetes resistant to azole agents, while having a little side effects.